PROJECT SUMMARY PROJECT III: FUNCTIONAL AND ANATOMICAL INVESTIGATIONS OF DOMAIN-SPECIFIC AND DOMAIN-GENERAL ALTERATIONS IN NEURAL SYSTEMS UNDERLYING MATH & READING DIFFICULTY The goal of this high-risk/high-reward project will be to investigate, using a new and novel perspective, the neural underpinnings of reading and math difficulties. In particular, in a novel theoretical conceptualization, this project links specific neural systems to specific behavioral characteristics exhibited by individuals with learning disabilities. The center within which this project is embedded focuses on three types of behaviors proposed to be altered in reading and math disability: processing speed, domain-specific processes that are needed to enable a given ability (e.g., word recognition for reading; numerical sense for math), and executive processes that aid in selecting and prioritizing specific information to support domain-specific processes. This project tests a model which posits that alterations of each of these three behaviors is associated with alterations in each of three specific aspects of neural function. The project will examine whether slowed processing speed, which is observed trans-diagnostically across reading and math disability, is associated with poorer overall integration and coordination of information across the brain. Brain organization will be assessed by state-of-the art methods. In one method drawn from graph theory, the brain is conceptualized as consisting as a set of nodes or regions, with the connections between them acting as a route for information flow (much like an airline network). The hypothesis to be tested argues that the first behavioral characteristic, slowed processing speed, will be associated with reduced efficiency of information flow through the brain. In the other method, the brain is divided into intrinsic connectivity networks, where brain regions whose activity co-varies together over time are grouped together (much as the world is composed of different alliances such as the European Union and North American Free Trade Association). From this perspective, it is proposed that in individuals with slowed processing speed, processing within these networks is not well insulated from one another. The project will also test the hypothesis that the second behavioral characteristic, domain-specific deficits (i.e., math difficulties, reading difficulties) are reflected in altered processing in brain regions critical to a given domain. In the case of reading, such critical areas include the language-related superior temporal/inferior parietal regions along with inferior frontal regions of the left hemisphere. For math, the critical region is the intraparietal sulcus. Finally, the project will test the hypothesis that those individuals with learning difficulty who also exhibit executive dysfunction, the third behavioral characteristic, will show alterations in function of lateral prefrontal regions, as well as disrupted connectivity of this region to posterior regions involved in domain-specific (e.g., math, reading) processing. So as to increase relevance for the identification and treatment of individuals with learning disability, an additional project goal will be to determine whether these neural markers can be used together with one another to predict the level of reading (or math) difficulties exhibited on an individual-by-individual basis. To meet these ambitious goals, the project brings together scientists with requisite areas of expertise.